PILOT PROJECT PROGRAM Director: Moon-shong (Eric) Tang, Ph.D. SIGNIFICANCE The four specific aims of this Pilot Project Program (PPP) are to: 1) promote the long-range research interests of the Center; 2) foster collaboration between Center members and the NYU community; 3) encourage Center investigators to explore new research initiatives; and 4) assist promising new investigators in establishing independent research in environmental health sciences. We have been very successful at achieving these four goals for the past ten years. The following are a few highlights of our successes in achieving these specific aims during the past five years. As one of the goals of this Center, efforts to understand the mechanisms of action, component composition, adverse health effects, mitigation and risks of ambient air exposures have been supported by a long and outstanding history in inhalation toxicology research. The PPP has worked diligently with Center faculty in achieving these goals. PPP funding has supported the establishment of a novel organ bath system that allowed for novel collaborative research conducted by Drs. L.-C. Chen and Lippmann in the assessment of the vascular function of aorta rings and small arteries. We have also provided PPP funding for the development of a new method of inhalation exposure: a fishing line system, that permits very small quantities of atmospheric particles to be used for nose-only exposure regimens. The novelty of this concept, the preliminary results generated by the collaborative work of Drs. Cohen and L.-C. Chen, along with the track record of these two researchers in collecting and studying World Trade Center (WTC) dust, have resulted in more than $2 million dollars of support from CDC/NIOSH to fund further research with WTC dust. We have supported Dr. Lippmann in determining the seasonal, regional, and local contributions to particulate matter (PM) composition in the New York City area, which is complemented by Drs. L.-C. Chen and Qu's study of the effects of PM composition on blood vessel damage and repair. The approaches, substantial results and the experimental designs supported and pioneered by these pilot research collaborations have reinforced the strengths of these investigators and laid a strong foundation, for the establishment of EPA and HEl funded PM Centers. In addition, the Center has a tradition of being a leader in understanding the molecular mechanisms of metal toxicity and carcinogenicity. The PPP has encouraged both classic epidemiological toxicology approaches and cutting edge molecular approaches to understanding the genetic and epigenetic roles in metal toxicity and carcinogenicity. The PPP supported Dr. Qu's research in identifying a variety of biomarkers that could be useful In large-scale epidemiological studies as markers for risk assessment in humans exposed to Cr(VI) at low ambient levels. The PPP also funded a new venture by Drs. Dai and Rossman in the determination of the effects of arsenic on the cell cycle and chromosomal stability. Also, we have supported two projects with multiple Pi's in the pursuit of understanding the effects of metals on epigenetics. In one pilot project, Drs. Wirgin, Costa, and Roy investigated the in vivo epigenetic effects of chromium, nickel, and arsenic exposure on histone marks in the early life-stages of fish. In another project, Drs. Costa and Qu examined, using ChlP-Seq, the long- and short-term effects of nickel exposure on gene expression by examining changes in H3K4 trimethylation and H3K9 dimethylafion throughout the human genome.